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Open AccessArticle

Genome-Wide Association Study of Opioid Cessation

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Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA 02118, USA
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Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA
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Department of Psychiatry, Washington University in St. Louis, St. Louis, MO 63130, USA
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School of Psychology, The University of Queensland, St Lucia QLD 4072, Australia
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School of Medicine, University of New South Wales, Sydney NSW 2052, Australia
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Perelman School of Medicine, University of Pennsylvania and VISN 4 MIRECC, Crescenz VAMC, Philadelphia, PA 19104, USA
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Departments of Psychiatry, Genetics and Neuroscience, Yale School of Medicine, New Haven, CT 06511, USA
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Department of Psychiatry, VA CT Healthcare Center, West Haven, CT 06516, USA
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Departments of Neurology, Ophthalmology and Epidemiology, Boston University Schools of Medicine and Public Health, Boston, MA 02118, USA
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(1), 180; https://doi.org/10.3390/jcm9010180
Received: 9 December 2019 / Revised: 20 December 2019 / Accepted: 3 January 2020 / Published: 9 January 2020
(This article belongs to the Special Issue Application of Opioids in Clinical Medicine)
The United States is experiencing an epidemic of opioid use disorder (OUD) and overdose-related deaths. However, the genetic basis for the ability to discontinue opioid use has not been investigated. We performed a genome-wide association study (GWAS) of opioid cessation (defined as abstinence from illicit opioids for >1 year or <6 months before the interview date) in 1130 African American (AA) and 2919 European ancestry (EA) participants recruited for genetic studies of substance use disorders and who met lifetime Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for OUD. Association tests performed separately within each ethnic group were combined by meta-analysis with results obtained from the Comorbidity and Trauma Study. Although there were no genome-wide significant associations, we found suggestive associations with nine independent loci, including three which are biologically relevant: rs4740988 in PTPRD (pAA + EA = 2.24 × 10−6), rs36098404 in MYOM2 (pEA = 2.24 × 10−6), and rs592026 in SNAP25-AS1 (pEA = 6.53 × 10−6). Significant pathways identified in persons of European ancestry (EA) are related to vitamin D metabolism (p = 3.79 × 10−2) and fibroblast growth factor (FGF) signaling (p = 2.39 × 10−2). UK Biobank traits including smoking and drinking cessation and chronic back pain were significantly associated with opioid cessation using GWAS-derived polygenic risk scores. These results provide evidence for genetic influences on opioid cessation, suggest genetic overlap with other relevant traits, and may indicate potential novel therapeutic targets for OUD. View Full-Text
Keywords: genome-wide association study; opioid cessation; opioid use disorder; shared genetic risk; polygenic risk score genome-wide association study; opioid cessation; opioid use disorder; shared genetic risk; polygenic risk score
MDPI and ACS Style

Cox, J.W.; Sherva, R.M.; Lunetta, K.L.; Johnson, E.C.; Martin, N.G.; Degenhardt, L.; Agrawal, A.; Nelson, E.C.; Kranzler, H.R.; Gelernter, J.; Farrer, L.A. Genome-Wide Association Study of Opioid Cessation. J. Clin. Med. 2020, 9, 180.

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